351185-23-4Relevant academic research and scientific papers
Novel 6-substituted benzoyl and non-benzoyl straight chain pyrrolo[2,3-d]pyrimidines as potential antitumor agents with multitargeted inhibition of TS, GARFTase and AICARFTase
Xing, Ruijuan,Zhang, Hongying,Yuan, Jiangsong,Zhang, Kai,Li, Lin,Guo, Huicai,Zhao, Lijuan,Zhang, Congying,Li, Shuolei,Gao, Tianfeng,Liu, Yi,Wang, Lei
, p. 531 - 541 (2017)
A novel series of 6-substituted benzoyl and non-benzoyl straight chain pyrrolo[2,3-d]pyrimidines were designed and synthesized as potential antitumor agents targeting both thymidylate and purine nucleotide biosynthesis. Starting from the key intermediate 2-amino-4-oxo-pyrrolo[2,3-d]pyrimidin-6-yl-acetic acid, target compounds 1–6 were successfully obtained through two sequential condensation and saponification reactions in decent yield. The newly synthesized compounds showed antiproliferative potencies against a panel of tumor cell lines including KB, SW620 and MCF7. In particular, most compounds of this series exhibited nanomolar to subnanomolar inhibitory activities toward KB tumor cells, significantly more potent than the positive control methotrexate (MTX) and pemetrexed (PMX). Along with the results of nucleoside protection assays, molecular modeling studies suggested that the antitumor activity of compound 6 could be attributed to multitargeted inhibition of folate-dependent enzymes thymidylate synthase (TS), glycinamide ribonucleotide formyltransferase (GARFTase) and 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase (AICARFTase). Growth inhibition by compound 6 also induced distinct early apoptosis and cell cycle arrest at S-phase, which resulted in cell death.
Synthesis and antitumor activity of a novel series of 6-substituted pyrrolo[2,3- d ]pyrimidines as potential nonclassical antifolates targeting both thymidylate and purine nucleotide biosynthesis
Liu, Yi,Zhang, Chuang,Zhang, Hongying,Li, Meng,Yuan, Jiangsong,Zhang, Yurui,Zhou, Jiaqi,Guo, Huicai,Zhao, Lijuan,Du, Yumin,Wang, Lei,Ren, Leiming
, p. 142 - 155 (2015)
A novel series of 2-amino-4-oxo-6-substituted pyrrolo[2,3-d]pyrimidines were designed and synthesized as potential nonclassical antifolates targeting both thymidylate and purine nucleotide biosynthesis. Condensation of 2,4-diamino-6-hydroxypyrimidine with ethyl-4-chloroacetoacetate and subsequent hydrolysis afforded the key intermediate, 2-amino-4-oxo-pyrrolo[2,3-d]pyrimidin-6-yl-acetic acid. Coupling with various amino acid methyl esters followed by saponification and condensation with 3-(aminomethyl)pyridine provided target compounds 1-9. The new compounds exhibited micromolar to submicromolar antiproliferative potencies against a panel of tumor cell lines including KB, A549 and HepG2. Growth inhibition of compound 2 toward KB cells resulted in cytotoxicity and G1/G2-phase accumulation, and was partially protected by excess thymidine and adenosine, but was completely reversed in the combination of thymidine and adenosine, indicating both thymidylate and de novo purine nucleotide synthesis as the targeted pathway. However, 5-aminoimidazole-4-carboxamide (AICA) protection was incomplete, suggesting inhibition of both glycinamide ribonucleotide formyltransferase (GARFTase) and AICA ribonucleotide formyltransferase (AICARFTase). The results of the docking studies show that 2 could bind and inhibit both thymidylate synthase (TS) and the two folate-dependent purine biosynthetic enzymes (GARFTase and AICARFTase), which is consistent with the results of in vitro metabolic assays. Our studies establish that compound 2 is an excellent lead analog as a multitargeted antifolate for further structure optimization.
Pyrrolo [2, 3 - d] pyrimidine compounds and their use
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Paragraph 0067-0069, (2018/05/16)
The invention relates to a pyrrolo [2,3-d] pyrimidine compound, pharmaceutically acceptable salt thereof and a medicinal composition containing the pyrrolo [2,3-d] pyrimidine compound, and also relates to use of the pyrrolo [2,3-d] pyrimidine compound in preparation of a medicine for treating a disease related to GARFTase inhibition activity, in particularly relates to application of the pyrrolo [2,3-d] pyrimidine compound in preparation of an anti-cancer treatment medicine.
Molecular recognition of a thymine bulge by a high affinity, deazaguanine-based hydrogen-bonding ligand
Ong, Hugo C.,Arambula, Jonathan F.,Rao Ramisetty, Sreenivasa,Baranger, Anne M.,Zimmerman, Steven C.
supporting information; experimental part, p. 668 - 670 (2009/06/05)
7-Deazaguanine (7-DeG) was developed as a hydrogen-bonding module capable of enhanced recognition of uracil (U) and thymine (T); a water-soluble derivative displayed high affinity and selectivity toward DNA and RNA duplexes containing single T- and U-bulg
